Confronting the Challenge of Antimicrobial Resistance

Drug resistance is making many diseases increasingly difficult -- and sometimes impossible -- to treat, according to Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

"Extensively drug-resistant tuberculosis and invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are just two recent examples of this problem that pose serious threats to domestic and global health," Fauci adds. In a new report in the Journal of Infectious Diseases, now available online, Fauci outlines NIAID's commitment to addressing this urgent public health issue.

The innate ability of microbes to evade containment and destruction by drugs through rapid reproduction and genetic mutation is exacerbated by the overuse and misuse of existing antimicrobial drugs, Fauci and his coauthors note. Other factors contributing to the upswing in drug resistance include a dearth of rapid diagnostic tests that would allow physicians to better gauge whether a given infection is drug-susceptible or drug-resistant, and a paucity of clinical trial data to guide therapeutic strategies.

NIAID is meeting the complex challenge of antimicrobial resistance through a multifaceted research approach that includes partnerships with other federal agencies, academia, industry and non-governmental organizations, the authors report. In fiscal year 2007, NIAID invested more than $800 million to support basic and translational research on antimicrobials, more than $200 million of which was devoted to understanding the causes, consequences and treatments of antimicrobial drug resistance.

Basic research projects under way at NIAID or in NIAID-supported labs across the country include the following:

-- Investigations of mechanisms of resistance and how these traits are acquired and passed on by microbes

-- Research on factors that contribute to the virulence of pathogens such as MRSA

-- Efforts to better understand and ultimately prevent biofilms slimy coatings made by communities of bacteria that are impervious to the effects of antibiotics

-- Creation of computer-based virtual microbial metabolic pathways that allow quick identification of potential drug targets

Facilitating the translation of basic research findings into better diagnostics, new therapies and novel strategies to slow the emergence of antimicrobial resistance is also an area of emphasis for the Institute, write the authors. The following are examples of the many applied and translational research programs supported by NIAID:

-- Numerous clinical trials, including one assessing the need for antibiotics in children with acute middle-ear infections; and two trials designed to test off-patent oral antibiotics for treating uncomplicated community-associated MRSA

-- Preclinical development of vaccine candidates to prevent staphylococcal infections

-- Efforts to improve diagnostics, particularly for healthcare-associated bacterial infections that are already or are likely to become drug-resistant, such as Clostridium difficile, Pseudomonas and Acinetobacter

-- DNA sequencing and other genomics resources that aid in discovery of diagnostics and therapeutics

Finally, the authors outline several new and established NIAID partnerships addressing antimicrobial resistance, including

-- The Federal Interagency Task Force on Antimicrobial Resistance, co-chaired by NIAID, the Centers for Disease Control and Prevention, and the Food and Drug Administration, which implements an annually updated action plan

-- The international Lilly Not-For-Profit Partnership for TB Early Phase Drug Discovery, which integrates the expertise of the pharmaceutical industry with university-based researchers to develop new drugs against TB, including multidrug-resistant and extensively drug-resistant forms of TB

-- A collaboration with the Novartis Institute for Tropical Diseases to advance new drugs to treat dengue fever

"With antimicrobial resistance, we face the perpetual challenge of maintaining a favorable balance between microbes and humans," says Fauci. "The efforts of NIAID and all our partners from the public health, research and pharmaceutical sectors are critical to addressing this challenge and thus keeping us at least one step ahead of our microbial foes."

In addition to Fauci, the other authors are N. Kent Peters, PhD, program officer for antibacterial resistance, NIAID Division of Microbiology and Infectious Diseases (DMID); Dennis M. Dixon, PhD, chief, Bacteriology and Mycology Branch, DMID; and Steven M. Holland, MD, chief, Laboratory of Clinical Infectious Diseases, NIAID Division of Intramural Research.

Reference: NK Peters et al. The research agenda of the National Institute of Allergy and Infectious Diseases in antimicrobial resistance. Journal Infect Dis. Published online March 2008.

Source: National Institutes of Health